1. Field of the Invention
The present invention relates to the isolation, characterization and use of a novel enzyme which belongs to a family of enzymes which catalyze the transfer of glucuronic acid from uridine diphospho-glucuronic acid to a wide variety of lipid soluble drugs, environmental chemicals and endogenous substances, and more particularly, to the characterization of, and isolation of the cDNA which encodes, a novel uridine diphospho-glucuronosyltransferase (UGT) (hereinafter UGT2B17) which has been found to conjugate androgenic compounds, particularly C.sub.19 steroids. The use of this enzyme in an assay is also described, as are several other uses of the DNA, fragments thereof, antisense fragments thereof and antibodies thereto.
2. Description of the Related Art
The enzymes identified as UGTs are a family of enzymes which catalyze the glucuronidation process in which glucuronic acid is transferred from uridine diphospho-glucuronic acid to a wide variety of lipid soluble drugs, environmental chemicals and endogenous substances such as bilirubin, steroid hormones and thyroxine. Generally, glucuronidation occurs in the liver and kidney and is responsible for the elimination of glucuronide derivatives from the body. However, UGT activity has also been identified in numerous tissues, including prostate, testis, skin, breast, brain and ovary tissues, and in breast and prostate tumor cell lines.
The UGT family of enzymes has been classified into two subfamilies, UGT1 and UGT2. The UGT1 family are generally known to be involved in the glucuronidation of planar and bulky phenol substrates and bilirubin, however, some members of the UGT1 family can conjugate estrogens. Enzymes of the UGT2 family are divided into two subfamilies, UGT2A which includes enzymes encoded by genes expressed in the olfactory epithelium and UGT2B which includes enzymes that catalyze the glucuronidation of bile acids, C.sub.19 steroids, C.sub.18 steroids, fatty acids, carboxylic acids, phenols and carcinogens, such as benzopyrene and 2-acetylaminofluorene. Several members of the UGT2B family have been isolated from human liver and been characterized. It has been found that there is an overlap in the substrate specificity among the UGT2B enzymes.
The present invention relates to a novel UGT which is a member of the UGT2B family and which is described in detail below.